Abstract: To determine the reason for an increase in tuberculin skin test (TST) conversion in employees in a nursing home and to determine the source case responsible for spread of tuberculosis (TB) in two nursing homes and a hospital in a rural part of Arkansas using molecular and traditional epidemiological methods. DESIGN: TB contact investigation of residents and employees of two nursing homes and a hospital. SETTING: Two nursing homes and a hospital in rural part of Arkansas. PARTICIPANTS: One hundred fifty-seven employees and 117 residents of two nursing homes and 211 employees of a hospital in rural part of Arkansas MEASUREMENTS: Tuberculin skin test. RESULTS: Analysis of room and work assignments of residents and employees who converted their TSTs in Nursing Home A showed that residents and employees in the same wing as the suspect source case were significantly more likely to have converted their TST than residents and employees in other wings ( P = .01). A nurse from the local hospital where the suspected source case had been sent developed a tuberculous cervical abscess, and one employee in Nursing Home A developed pulmonary TB. A visitor to Nursing Home A was diagnosed with culture-positive pulmonary TB 2 years later. Genotyping of the Mycobacterium tuberculosis isolates from the four secondary cases showed identical patterns. CONCLUSION: Molecular and traditional epidemiological studies revealed an outbreak of TB that began in a nursing home and spread to a second nursing home, a local hospital, and the community.